Abstract

Introduction: Most models estimating risk of carrying germline BRCA mutations are based on family history and age of cancer onset. Additional histologic criteria may be useful to identify patients at risk for harboring BRCA1 mutations. BRCA1 positive breast tumors are significantly more often estrogen receptor, progesterone receptor, and erbB-2 (HER2-neu) negative (“triple negative” (TN)) and are strongly associated with a basal phenotype confirmed by DNA microarray. Basal-like tumors express cytokeratins 5,6, and 14 or 17 by immunohistochemistry (IHC). It is unknown whether testing for BRCA1 mutations in TN basal-like breast cancer patients will identify additional carriers of mutations in this gene.Methods: A retrospective evaluation of patients with triple negative breast cancer seen at Cooper Cancer Center between 2004 and 2006 was performed after IRB approval. IHC was performed to identify the subset of basal-like breast cancers.Results: A total of 89 women were identified as diagnosed with TN breast cancer, while 53 had pathology available for review. 21 patients were identified as basal phenotype, whereas 32 were non-basal. Of the 21 patients who had basal-phenotype tumors, six underwent genetic testing and 3 were found to have a deleterious BRCA1 mutation. Of 32 non-basal patients, 9 patients underwent genetic testing and 2 were found to have a deleterious BRCA1 mutation. There was no difference between basal subtype and BRCA1 postivity [Fisher's Exact Test p=0.32]. Of note, 1of 5 (20%) patients with basal phenotype had no family history but tested positive for BRCA1 mutation and would have been missed by relying on conventional methods.Conclusion: Although there is a trend towards a higher percentage of TN breast cancer patients with basal subtype having BRCA 1 mutations (50 vs 22%), this was not found to be statistically significant (Fisher's exact p=0.32). However, this dataset is limited by a small sample size. Only 40% of TN breast cancer patients had a basal phenotype by IHC in this study, while other studies have shown 70- to 85% rate. Ongoing evaluation of patients with basal-like subtype and triple negative tumors should continue to investigate this relationship, especially in light of newer therapeutics that may impact this population. This data also suggests that patients with basal phenotype and triple negative disease should be considered for referral for genetic testing even in the absence of family history.